ProjectSummary Supportisrequestedforaunique,international,multidisciplinaryconferenceentitledKININ2018CLE organizedbyAlvinH.Schmaier,KeithRMcCrae,EviX.Stavrou,MarvinNieman,SadashivaS.Karnik,and JacksonTWrightofCaseWesternReserveUniversity(CWRU).ThismeetingwillbeheldinCleveland, OhioontheCWRUcampusfromJune17th-20th,2018.Thegeneraltopicofthismeetingisrelevanttothe NHLBImissionsinceitcelebratesthegrowthofknowledgeinseveralcomponentsoftheplasmacontact, kallikrein-kinin,andreninangiotensinsystemsandthetranslationofthatknowledgeintotherapeutictargets forseveralcardiovasculardiseases.Thecontactactivationandplasmakallikrein-kininsystemhavelong beenrecognizedtoproducebradykininandinfluencebloodcoagulation,inflammation,fibrinolysis, complementandtherenin-angiotensinsystems.Thesesystemsconsistofbiologicallyactivepeptides(e.g. bradykinin,angiotensinII,angiotensin1-7),theirG-protein-coupledreceptors(angiotensinreceptor1and2, bradykininreceptor1and2,andMas),theenzymesthatproducethesebiologicpeptides[factorXIIa, plasmakallikrein,renin,angiotensinconvertingenzymes,prolycarboxypeptidase,neutralendopeptidase (neprilysin)],anditsnaturalinhibitorC1inhibitor.Inrecentyears,thelistofdisordersthataremanagedby targetingmembersofthesesystemshasextendedfromhypertensiontoheartfailure,hereditary angioedema,andarterialthrombosisinhibitionwithoutriskofhemorrhage.Thismeetingisuniquebecause itwillbringtogetherthoughtleadersindiversefieldstofillgapsinknowledge,tocommunicateideasand buildnewassociations,andtoforgenewcollaborationsinacademiaandindustry. Thisconferencegrant(R13)applicationrequestsfundsfortravelawardsfortrainees(pre-doctoralstudents, post-doctoralstudents,instructors,orassistantprofessors)forconferenceregistration,travel,andhotel. Theseinternationalkininconferencesareheldeverythreeyearsindifferentlocations.Thelasttimeitwas heldintheUnitedStateswasin2002inCharleston,SouthCarolina.Sincethattime,anewgenerationof investigatorshasdevelopedduetoseveraldiscoveries:1)allmurinemodelsofcontactproteinsinfluence thrombosisriskwithoutbleeding;?2)multiplenoveltargetshavebeenusedtoreducebradykininformationin themanagementofhereditaryangioedema;?3)previouslyunappreciatedbiologicmechanismsforfactorXII activationhavebeenrecognized;?and4)neprilysincombinedwithangiotensinreceptor1antagonisthave beenrecognizedasapotentcombinationofagentstotreatheartfailure.Theresearchmomentuminthese fieldshasbeenextraordinaryanddrivestheneedforthisinter-disciplinaryconference. ThegoalsofKININ2018CLEareseveralfold:1)Disseminatetheresearchandclinicalprogressinkinin biologysincethelastmeetingintheUnitedStates;?2)Bringtogethertheworld?sbestinvestigatorsinthe fieldofkininsforsharingresearchandgenerationofnewideastofillgapsinknowledgeforfuture investigation;?3)Encouragefertilizationofcross-disciplineresearchtostimulatenewideasandunique researchopportunities;?4)Emphasizethoseareaswherekininscienceisnowbeingtranslatedintoclinical use;?and5)Inspirethenextgenerationofjuniorinvestigatorsinthisfieldtoachievethatwhichtheir teachersandmentorswereunabletoaccomplish. KININ2018CLEobjectivesareseveral-fold:1)Fostercommunication,sharingofideas,andfuture collaborationsamongparticipants;?2)Clarifyunknownsinthefieldsandinfusenewknowledgewithre- interpretationsofolderinformation;?3)Educateanewgenerationofinvestigatorsinthesecontentareas;?4) Supportcareerdevelopmentofnewinvestigatorsinthefield;?5)Stimulatecollaborationbetweenacademia andindustry;?6)Stimulatethepharmaceuticalindustryinterestinnewareaswherethereispotentialfor developmentoftherapeutictargets.ThesuccessofKININ2018CLEwillbemeasuredbyseveralevaluating tools:1)Wewillevaluateeachspeakerforobjectivity,quality,andlackofcommercialbiasinthe presentation;?2)Anoverallmeetingevaluationwillbeperformedatconferenceconclusion;?3)Ameeting reportthatwillbepublishedinFrontiersinHematology;?4)Anon-linesymposiumofeachspeaker?s presentationwillbepublishedinFrontiersinHematologywithin12monthsoftheconference;?5)Wewill ascertainthenumberofabstractspeakerswhowerejunior(pre-andpost-doctoralstudents,instructors assistantprofessors)incareerdevelopment.Insum,thisconferenceintendstobringtogetherawide numberofinvestigatorsinkinin-relatedbiologytofostercommunication,collaboration,andgrowthofthe fieldinyounginvestigatorsandcontinuedtranslationintotherapiesforanumberofdisordersrelevanttothe missionofNHLBI.